Chemotaxis is broadly defined as the orientation or movement of a cell or organism in relation to a chemical factor (Harris, 1954; Armstrong, 1985). Certain cells are capable of sensing a particular chemical factor and, in response, migrating toward or away from higher concentrations of the substance. In recent years, researchers and clinicians have expended great effort in studying cell motility for a number of cell types. Oftentimes, for example, it is useful for a clinician to determine the motility (e.g., ascertain whether the response is normal or depressed) of immune cells from patients suffering from disease, or to measure the motility of sperm for infertility patients.
Traditionally, the most popular assays for measuring cellular chemotaxis have utilized a so-called "Boyden chamber" (Boyden, 1962), or similar apparatus, in which the cells migrate through a filter that has pore openings that are smaller than the cell diameter. Typically, cells of a particular type are placed in a chamber on one side of the filter and a chemotactic agent is placed in a chamber on the other side. Results are usually quantified by counting the number of cells that have migrated through the filter. While such techniques are reasonably simple and widely available, they are associated with certain disadvantages. For example, they typically require a large number of highly purified cells. Isolating the cells, setting up the apparatus, and counting the cells which have migrated can be very labor intensive. Frequently, the process of isolating the cells can require several hours. Moreover, the cells are sometimes damaged during the process. For rare cell types, of course, the task of isolating a sufficiently large number of cells for use in the assay can be especially difficult and time consuming.
With most conventional chemotaxis assays, the process of examining and counting the cells that have moved has also been tedious and time-consuming. This is particularly true for assays that have relied upon manual examination, counting and analysis. Although some chemotaxis assays have automated, to varying degrees, these processes, they have not been entirely satisfactory either. For example, certain chemotaxis assays have employed automated readers of the type that detect the bulk amount of radiation emitted from a sample, e.g., a densitometer, fluorimeter, or spectrophotometer. While useful for determining the overall number of labeled cells in a region, such devices are not able to provide information regarding the positions of individual cells. Thus, it is not possible to image or map individual cells using such devices.
As another disadvantage, conventional cell-motility assay devices are not capable of simultaneously processing a large number of separate samples. In fact, most of the known assays accommodate only a single sample at a time. Of course, in situations where it is desirable to assay numerous samples in a relatively short time period, e.g., certain commercial research and clinical labs, the limited capacity of the known assay devices, which places a ceiling on throughput and productivity, can be a serious problem. Although a few multiple-site assays have been developed that can accommodate a plurality of samples at once, the total number of samples that can be simultaneously assayed is typically quite limited (e.g., less than 100). Moreover, the known multiple-site assays continue to suffer the disadvantages discussed above, e.g., their set-up and operation are tedious and labor-intensive, and they are not capable of providing positional information on individual cells.